Phenols palladium-catalyzed arylations

The palladium-catalyzed arylation of 2-phenylphenols and naphthols shows an interesting feature of arylation of C-H bonds, leading to the formation of an (aryl)(aryloxy)palladium(n) intermediate.65,65a,65b The phenolates are suitable as precoordinating groups. The reaction of 2-hydroxybiphenyl with an excess of iodobenzene occurs regioselectively at the two ortho-positions of phenyl group under palladium catalysis (Equation (57)). In the case of 1-naphthol, the peri-position is phenylated (Equation (58)). 

In contrast with arylations of other heterocycles, the palladium-catalyzed arylation of benzoxazoles at C-2 proceeds readily at ambient temperature (Scheme 11.21) [67]. Although, as in other cases no kinetic isotope effect was found for 59a, a Hammett plot revealed a correlation with ct with a positive p, which indicates that a phenolate intermediate is formed in this reaction. Therefore, this reaction has been shown to proceed by a totally different mechanism. According to experimental results and DFT calculations, the reactions proceed by the deprotonation of benzoxazoles 59 to form 61, which is in equilibrium with o-phenoxyisocyanide 62. Coordination of the oxidative addition product PdI(Ph)L2 to the isocyanide then forms 63 which cyclizes to form palladate 64, from which the 2-phenylbenzoxazoles 60 are formed by reductive ehmination. 

A palladium-catalyzed arylation of TBDPS-protected 2-bromophenols and 2-bromoanilines via C-H activation vras reported in 2009. Moderate to good yields of the desired six-membered silicon-containing heterocyclic compounds were produced (Scheme 3.18). After deprotection with F , the corresponding 2-phenyl phenols or 2-phenyl anilines were formed. 

Zhang and coworkers have reported on a palladium-catalyzed carbon-sulfur cross-coupling of aryl perfluoroalkoxysulfonates with thiols (Scheme 7.78) [91]. The fluorous substrates were obtained from commercially available phenols by treatment with perfluorooctanesulfonyl fluoride (C8F17S02F) under basic conditions. Various thiols were reacted with a slight excess of the perfluorinated sulfonates in a... 

The preparations of aryl sulfides typically employ aryl halides as starting materials. The procedure described here makes use of the ubiquitous class of commercially available phenolic compounds in the form of aryl triflates, which expands the range of readily accessible aryl sulfides. Prior to this disclosure, the use of aryl triflates in a palladium-catalyzed process for the formation of aryl alkyl sulfides was unprecedented. This procedure appears to be general with regard to electronically neutral or electron-deficient aryl triflates (Table 1). The yields in Table I correspond to the initially disclosed procedure employing sodium (ert-butoxide as the base. Lower yields were obtained with the 4-nitro-... 

The 4- and 6-positions of pyrrolo[2,3-3]pyridines can be substituted via palladium-catalyzed cross-coupling reactions with the 4- or 6-halo-substituted derivatives (Scheme 3) <2001SL609>. Nucleophilic displacement of the 4-substituent of 6-chloro-4-nitro- and 4,6-dichloro-pyrrolo[2,3-/ ]pyridines takes place with phenols. Protection of the pyrrole nitrogen with a /3-trimethylsilylethoxymethyl (SEM) group affords good yields of the aryl ethers (Equation 3) <2006TL2069>. 

Although the substrate scope for the palladium-catalyzed aminations of aryl halides was improved by the use of weaker bases, these procedures still had limitations. First, the reactions were typically slower and required higher levels of catalyst than those with f-BuONa as base. Second, reactions of substrates containing alcohol, phenol or amide functional groups have been difficult to accomplish. Recently, Buchwald and coworkers... 

Phenols, much like anilines, represent important synthons for the constraction of biologically active compounds and functional materials. " Moreover, the phenol moiety itself is present in a number of top selling pharmaceuticals with diverse function selected examples are depicted in Figure 3. The use of water, or related MOH salts, as nucleophiles in palladium-catalyzed cross-couplings involving (hetero)aryl halides conceptually represents a mild and selective route to phenols that is complementary to more established phenol syntheses, " " including oxidative protocols. However, the difficulties associated with realizing such transformations mirror those... 

In connection with a total synthesis of frondosin B, the key intermediate shown below was synthesized by a sequential reaction of the phenol, the enyne and the bromide in a one-pot operation as shown <04OL457>. The palladium-catalyzed intramolecular C-0 bond formation between aryl halides and enolates was employed to make 2,3-disubstituted benzo[i> furans <04OL4755>. 

Palladium-catalyzed carbonylation of aryl triflates in the presence of an alcohol141 or amine1423 provides a good method for preparation of arenecarboxylic esters and amides from phenols (equation 121). However, palladium-catalyzed cyanation of 5,6,7,8-tetrahydro-2-naphthyl triflate with potassium cyanide failed completely whereas the more reactive tetrakis(triphenylphosphine)nickel(0) could catalyze the same reaction which gives the nitrile in a good yield142b (equation 122). 

Biaryl structures are found in a wide range of important compounds, including natural products and organic functional materials [8,80,81]. One of the most common and useful methods for preparing biaryls is the palladium-catalyzed coupling of aryl halides with arylmetals (Scheme 1, mechanism A). On the other hand, aryl halides have been known to couple directly with aromatic compounds as formal nucleophiles under palladium catalysis. While the intramolecular cases are particularly effective, certain functionalized aromatic compounds such as phenols and aromatic carbonyl compounds, as well as... 

In recent years, significant efforts have been made to extend the scope of palladium-catalyzed aminations with respect to the leaving group on the electrophile, with particularly attention being focused on the esters of various acids [2, 3j. The main motivations for these developments were the good availability of the phenols as precursors, along with their usually low cost when compared to aryl halides. Further, the substitution pattern of the phenols is often complementary to that of available aryl halides. 

Meyers and colleagues described the palladium-catalyzed carbonylative synthesis of oxazolines as early as 1992 [268]. Aryl or enol triflates made from the corresponding ketones and phenols, and also aryl halides, were used as starting materials and coupled with amino alcohols to give chiral a,)S-unsaturated or aryl oxazolines in good yields. Later on, Perry s group performed systematic studies on this one-pot, two-step process for the preparation of oxazolines (Scheme 2.37) [269, 270]. 

Since aryl triilates can easily be generated from corresponding phenols, Beller also developed a palladium-catalyzed carbonylative Sonogashira coupling of aryl triflates in 2010 [50]. This is the first carbonylative Sonogashira protocol that can apply aryl triflates as substrates. Various alkynones were produced in moderate to good yields under low pressure of CO (Scheme 5.21). A one-pot synthesis of enaminones was also achieved by running the reaction in the presence of primary amines. 

---